Neurofibromatosis Type 2 and Its Head and Neck

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Acta Otorrinolaringol Esp. 2014;65(3):148---156
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ORIGINAL ARTICLE
Neurofibromatosis Type 2 and Its Head and Neck
Manifestations: Literature Review and Population
Study in the Community of Cantabria and the Province
of Las Palmas夽
Gloria Guerra-Jiménez,a,∗ Pilar Camargo Camacho,b Ángel Ramos-Macías,a
Carmelo Morales Anguloc
a
Servicio de Otorrinolaringología, Complejo Hospitalario Insular Materno Infantil (CHUIMI), Las Palmas de Gran Canaria, Spain
Servicio de Otorrinolaringología, Hospital Universitario de Gran Canaria Dr. Negrín (HUGCDN), Las Palmas de Gran Canaria, Spain
c
Servicio de Otorrinolaringología, Hospital Universitario Marqués de Valdecilla (HUMV), Santander, Spain
b
Received 2 October 2013; accepted 9 December 2013
KEYWORDS
Neurofibromatosis
type 2;
Head and neck;
Ear, nose and throat
manifestations
Abstract
Introduction and objectives: Neurofibromatosis type 2 (NF2) is an infrequent autosomal dominant disease characterised by the appearance of VIII nerve schwannomas, meningiomas and
ocular abnormalities. Incidence of 1:25 000 and prevalence above 1:80 000 are estimated in general. The objectives of our study were to determine current prevalence of NF2 in the Community
of Cantabria and the province of Las Palmas, and its head and neck manifestations.
Material and methods: This was a population-based, retrospective study in 3 tertiary hospitals.
Results: The study population showed prevalence of 1:600 000 in the Community of Cantabria
and 1:280 000 in the province of Las Palmas. The most frequently diagnosed tumour was acoustic
neuroma (n = 15), followed by trigeminal neurinoma (n = 2) and vagus (n = 1).
Conclusions: Cases of NF2 are infrequent in Cantabria and Las Palmas, lower than that reported
in the literature. The most frequently described head and neck tumour in the literature is
acoustic neuroma, followed by schwannoma of cranial nerves V and X. Other tumours such
as nasal, laryngeal, chorda tympani or cranial nerve VII schwannomas are also described. The
most frequent ENT manifestation is hearing loss, especially unilateral, followed by cervical
mass, tinnitus and headache. Early diagnosis and multidisciplinary management in specialised
centres could improve life expectancy and quality of life for these patients.
© 2013 Elsevier España, S.L. All rights reserved.
夽 Please cite this article as: Guerra-Jiménez G, Camargo Camacho P, Ramos-Macías Á, Morales Angulo C. Neurofibromatosis tipo II y sus
manifestaciones en cabeza y cuello: revisión bibliográfica y estudio poblacional en la Comunidad de Cantabria y la provincia de Las Palmas.
Acta Otorrinolaringol Esp. 2014;65(3):148---156.
∗ Corresponding author.
E-mail address: gloriaguerraj@gmail.com (G. Guerra-Jiménez).
2173-5735/$ – see front matter © 2013 Elsevier España, S.L. All rights reserved.
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Literature Review and Population Study of Type 2 Neurofibromatosis
PALABRAS CLAVE
Neurofibromatosis
tipo ii;
Cabeza y cuello;
Manifestaciones
otorrinolaringológicas
149
Neurofibromatosis tipo ii y sus manifestaciones en cabeza y cuello: revisión
bibliográfica y estudio poblacional en la Comunidad de Cantabria y la provincia
de Las Palmas
Resumen
Introducción y objetivos: La neurofibromatosis tipo ii (NFII) es una enfermedad infrecuente de
herencia autosómica dominante que se caracteriza por la aparición de schwanomas del viii par,
alteraciones oculares y meningiomas. Se estima una incidencia de NFII de 1:25.000 y una prevalencia mayor de 1:80.000. Los objetivos de nuestro estudio fueron determinar la prevalencia
puntual de NFII en la Comunidad de Cantabria y la provincia de Las Palmas, así como caracterizar
sus manifestaciones de cabeza y cuello.
Material y métodos: Se trata de un estudio poblacional, retrospectivo, en 3 hospitales de tercer
nivel.
Resultados: El estudio poblacional mostró una prevalencia puntual de 1:600.000 en la Comunidad de Cantabria y 1:280.000 en la provincia de Las Palmas. El tumour más frecuentemente
diagnosticado fue el neurinoma del acústico (n = 15), seguido del neurinoma del trigémino (n = 2)
y del vago (n = 1).
Conclusiones: La NFII en Cantabria y Las Palmas es infrecuente, menor a la descrita en la
literatura. El tumour de cabeza y cuello más frecuentemente descrito en la literatura es el
neurinoma del acústico seguido del schwanoma del v y del x par. Están descritos aisladamente
otros tumores, como el schwanoma nasal, laríngeo, de chorda timpanae o del vii par. La manifestación ORL más frecuente es la hipoacusia, sobre todo unilateral, seguida de masa cervical,
acúfenos y cefalea. Un diagnóstico precoz y el manejo multidisciplinar en centros especializados
podrían mejorar la esperanza y calidad de vida en estos pacientes.
© 2013 Elsevier España, S.L. Todos los derechos reservados.
Introduction
Neurofibromatosis (NF) is a hereditary disease of autosomal dominant transmission. NF type I or Von Recklinghausen
disease, associated to a defect in chromosome 17, is characterised by the appearance of ‘‘coffee with milk’’ stains,
neurofibromas on the skin, hamartomas of the iris and
cognitive deficit, with the appearance of vestibular neuromas being rare. NF type II (NF-II), secondary to a defect
in chromosome 22, is characterised by the appearance of
schwannomas of the 8th cranial nerve, as well as ocular
alterations and meningiomas. Although less often that in
patients with NF type I, ‘‘coffee with milk’’ stains and neurofibromas on the skin can appear.
The use of diagnostic criteria, specific molecular tests
to identify mutations, and the development of nuclear
magnetic resonance imaging (NMRI) have brought about an
increase in the diagnosis of this disease. Initially, the incidence of NF-II was calculated to be 1:30 000---40 000, with
approximate prevalence of 1:200 000, but recent studies
estimate an incidence of 1:25 000 and prevalence greater
than 1:80 000.1---3 However, there are no recent population
studies that analyse the prevalence and incidence of this
disease in the Spanish population.
The onset of NF-II is usually in the later years of adolescence or at the beginning of adulthood, although cases of
presentation between the first year of life and the seventh
decade have been described. The most common symptoms are the appearance of neurological, ocular (posterior
subcapsular cataract, epiretinal membranes and retinal
hamartomas) and cutaneous (intradermic plaques and subcutaneous and cutaneous tumours lesions).
Among the neurological lesions, the most characteristic are bilateral vestibular schwannomas that develop
around 30 years of age (90%---95%). Initial symptoms
include tinnitus, hearing loss and alterations in balance
that begin insidiously; however, hearing loss may occur
suddenly.4 Facial paralysis is seldom produced. If not
treated, the schwannoma leads to brain compression and
hydrocephaly.4
Schwannomas can also appear in other cranial nerves
(24%---51%), intracranial meningiomas (45%---77%), intra- and
extramedullary spinal tumours, such as astrocytoma or
ependymoma (63%---90%), and peripheral mononeuropathy in
the form of partially recovered facial paralysis, strabismus,
or fallen foot or hand (>66%).4
Diagnostic criteria were initially established in the conference of the National Institutes of Health Consensus in
1988.5 They were later substantially modified in the criteria
of Manchester, Evans6 and Baser et al.,7 which significantly
improved diagnostic sensitivity, without affecting specificity.
At present, molecular diagnosis of NF-II is carried out
using the analysis of unusual mutations of the gene NF2,
located in the long arm of chromosome 22 and producer of
merlin or schwannomin, a membrane protein that acts as
a tumour suppressor. This mutation can be found in 90% of
the families with NF-II. In individuals carrying de novo mutation produced after ovular fertilisation, the existence of cell
mosaicism is possible in 25%---33%, which can delay molecular
diagnosis until the tumour tissue is analysed.8
Treatment for the various symptoms of NF-II is similar
for sporadic tumours of the same type. However, multidisciplinary management is obligatory to minimise disabilities
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150
and to avoid morbidity secondary to treatment of these
tumours.
The objectives of our study were to estimate the prevalence of NF-II in our community, as well as to characterise
the symptoms of this disease in the head and neck area.
Material and Methods
Environment and Subjects
This was an observational retrospective study on the population of Cantabria and the province of Las Palmas, from
which we drew the patients diagnosed and in follow-up for
NF-II in their corresponding centres of reference. The study
involved 3 level-3 hospitals: Hospital Universitario Marqués
de Valdecilla (HUMV), referral hospital in the Community
of Cantabria; the Complejo Hospitalario Universitario Insular Materno Infantil (CHUIMI), referral hospital in the south
of Gran Canaria island and of Fuerteventura island; and the
Hospital Universitario de Gran Canaria Dr. Negrín (HUGCDN),
referral hospital for the north of Gran Canaria island and
Lanzarote island.
Design
The design was retrospective observational.
Instrumentation
To perform the population study, information was gathered
on the case histories of the patients with NF-II. The recompilation of the cases was carried out with the collaboration
of the Coding Service in all the centres and, in the HUMV,
with the additional review of the cases gathered in a specific file belonging to the Neurology Service. A total of
166 case histories (46, 34 and 86 in HUGCDN, CHUIMI and
HUMV, respectively) were reviewed, with diagnoses coded
as ‘‘neurofibromatosis type II’’, ‘‘neurofibromatosis’’ and
‘‘non-specific neurofibromatosis’’ and the cases of NF-II
were pulled. All of the patients fulfilled the diagnostic criteria for NF-II established by Evans6 in 2009 (Table 1).
Clinical and demographic variables were recorded: family
history of NF-II, personal history, age at diagnosis, otorhinolaryngological (ORL) symptoms shown at any point in the
disease and treatment received. The appearance of tumours
in any location was documented. Treatment received was
gathered distinguished between that of conservative or
expectant type, unilateral or bilateral surgery unilateral or
bilateral stereotactic therapy. The application of rehabilitative measures was investigated, especially those carried out
on audition or facial motility. If a gene study was performed,
its results were recorded.
Statistical Analysis
The data were stored and treated using OpenOffice tools.
Results
The population study yielded 3 cases diagnosed and
followed-up in the HUMV between January 1970 and April
G. Guerra-Jiménez et al.
Table 1 Neurofibromatosis Type II Diagnostic Criteria
(Including the Criteria of National Institutes of Health and
Others).
1. Bilateral vestibular neurinomas
2. First-degree relative with NF-II and:
a) unilateral vestibular neurinoma, or
b) 2 of the following:
Meningioma
Schwannoma
Glioma
Neurofibroma
Posterior subcapsular lens opacity
3. Unilateral vestibular neurinoma and 2 of the following:
a. Meningioma
b. Schwannoma
c. Glioma
d. Neurofibroma
e. Posterior subcapsular lens opacity
4. Multiple meningiomas and:
a. Unilateral neurinoma, or
b. 2 of the following:
Schwannoma
Glioma
Neurofibroma
posterior subcapsular lens opacity
Source: Evans.6
2013, 2 of whom were deceased at the time of the study:
the first showed disseminated NF-II with cerebral meningeal
implants, implants in the left cranial nerves V and VIII and
multiple intradural implants in the cervical, dorsal and lumbar regions; the patient died 11 months after the diagnosis,
from severe intraventricular haemorrhage. The time and the
cause of death are not documented for the second case.
Considering the cases of NF-II alive at the time of the study
in comparison to the reference population, NF-II prevalence in the Community of Cantabria was estimated to be
1:600 000 inhabitants.
In the HUGCDN 5 cases were recorded from 1994 to June
2013, 2 of which were deceased at the time of the study
from unknown causes: clinical data could not be compiled
on the first case; the second patient died at the age of
44 years, 17 years after diagnosis. In the CHUIMI there was
only a single case of NF-II registered from 2005 to June 2013.
Considering the NF-II cases alive at the time of our review in
comparison to the population of reference, NF-II prevalence
was estimated to be 1:280 000 in the province of Las Palmas.
The characteristics of all the cases registered are shown
summarised by hospital in Table 2.
Family history of NF-II was only confirmed in 2 cases. In
Case 8, from the CHUIMI, heterozygosis of the IVS12.2A>G
mutation was found in intron 12 of the NF-II gene (22q12).
This patient had a history of brain tumours of unknown origin
in a grandfather and in 2 paternal great-uncles. Case 2, from
the HUMV, had family history of NF-II, but a gene study was
not available.
Table 3 shows a summary of the types of tumours in the
ORL area presented in our series, by hospital.
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Literature Review and Population Study of Type 2 Neurofibromatosis
Table 2
151
Cases Series Presented in the Community of Cantabria and the Province of Las Palmas.
Case
Age,
gender
Symptoms
Tumours
Treatment
Sequelae
Centre
1
32 y, M
Horizontal
diplopia,
hemi-facial
paresthesias
Middle
laminectomy
C5-C7; CHT:
ifosfamide x9;
adriamycin
docetaxelgemcitabine
x2
Haematological
toxicity
HUMV
2
25 y, M
Surgical (not
specified)
Bilateral
cophosis
3
30 y, F
Bilateral
hearing loss,
tinnitus,
imbalance,
V par
Hearing loss,
intermittent
imbalance,
cervical mass,
dysphonia
Intradural C5-C7
neurofibrosarcoma; cerebral
meningeal
tumoursa ; left V
and VIII cranial
nerve tumoursa ;
dorsal and lumbar
intradural
tumoursa
Bilateral VIII
cranial nerve
neurinoma
Left Neurinoma
VIII par:
stereotactic
surgery; right
neurinoma VIII
par: surgery,
suboccipital
approach + adjuvant
radiosurgery;
neurinoma del X:
cervicotomy
Left: severeprofound
hearing loss.
Right cochlear
implant; right:
imbalance,
cophosis and
paralysis VII.
Upper
palpebral
prosthesis.
Temporoorbicular
plasty of fascia
lata
4
27 y, M
Progressive
SNHL
Obv (y); Right:
SFM; Left: SSO
Right FP
5
49 y, F
SNHL,
imbalance
Obv (2 y)
-
6
39 y, F
SNHL
Right: obv (24 m),
SFM; Left: obv
(y), S
Right FP
7
16 y, F
Progressive
right SNHL
Right: obv (4 y),
STLB + CI; Left:
Obv (m), S
-
Meningiomas: left
side sphenoid,
dorsal D2-3, right
frontal and right
MCF;
bulbo-medullary
astrocytoma;
ovarian
micropapillary
mucinous
cystadenoma;
bilateral VIII
cranial nerve
neurinoma;
neurinoma of the
right vagal nerve
Bilateral VIII
cranial nerve
schwannoma
Bilateral VIII
cranial nerve
schwannoma
Bilateral VIII
cranial nerve
schwannoma;
right eye
neurofibroma;
meningioma
parietal;
cutaneous
neurofibromas
Bilateral VIII
cranial nerve
schwannoma;
cervical and
foramen magnum
neurinoma; frontal
meningiomas
HUGCDN
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152
G. Guerra-Jiménez et al.
Table 2 (Continued)
Case
Age,
gender
Symptoms
Tumours
Treatment
Sequelae
Centre
8
12 y, V
Dorsal pain
Ependymoma;
right tentorial
meningioma and
left parasagittal
parietal;
schwannomas:
cutaneous nasal,
cutaneous
infraorbital,
bilateral VIII, left
V and right X
cranial nerves
(recurrent
laryngeal nerve)
Left: SRS; right:
radiosurgery
Left cophosis
CHUIMI
CHT: chemotherapy; CHUIMI: Complejo Hospitalario Universitario Insular Materno Infantil; F: female; HUGCDN: Hospital Universitario de
Gran Canaria Dr. Negrín; HUMV: Hospital Universitario Marqués de Valdecilla; M: male; m: months; Obv: observation; PF: facial paralysis;
S: surgery not specified; SFM: surgical treatment using fossa media approach; SNHL: sensorineural hearing loss; SRS: surgical treatment
using retrosigmoid approach; SSO: surgical treatment using sub-occipital approach; STLB + CI: surgical treatment using translabyrinthine
approach plus cochlear implant in the same operation; y: years.
Tumours in the ORL area are indicated in bold type. The columns coloured grey show the patients deceased at the time of the study.
a Non-biopsied tumours.
Discussion
NF-II is a rare clinical entity. According to recent studies, incidence of 1:25 000 and prevalence greater than
1:80 000 are estimated.1---3 Prevalence in the Communities
of Cantabria and the province of Las Palmas turned out to
be significantly less than expected.
The tumours that appeared in our patients coincided
with the most frequently found in the literature: based
on our review, the most frequent head and neck tumour
in NF-II is the acoustic neurinoma9---12 (n > 100), followed
by schwannoma of the V cranial nerve (n = 56)13---20 and of
the X nerve (n = 4).20 In our series there were bilateral
and unilateral cases of acoustic neurinoma (15), trigeminal nerve (2) and vagal nerve neurinoma (1). Other types
of tumours in the ORL area have been described, such as
nasal schwannoma21,22 and laryngeal schwannoma23---25 or
neurofibroma.26 It is rare to see the appearance of other
tumours such as schwannoma of the tympanic cord27 and
of the facial nerve itself,28,29 as well as meningiomas of the
olfactory bulb21 and of the IX,20 XI20 or XII20,30 cranial nerves.
Table 3
The various ORL tumours described in the literature appear
summarised and by order of frequency in Table 4.
The ORL symptom most frequently reported in the literature on NF-II is hearing loss (66%)---more frequently
unilateral, followed by cervical mass31 (10%), imbalance,
tinnitus and headache (6%). Other less frequent symptoms
are dysphagia, dyspnoea, laryngeal mass, facial paresis, nasal mass (4%) or the appearance of pneumosinus
dilatans.32 The various forms of ORL presentation of NF-II
described in the literature are shown ordered by frequency
in Table 5.
The diagnosis of schwannoma should be suspected in
the presence of asymmetrical sensorineural hearing loss
confirmed by liminal tone audiometry. Auditory provoked
potentials can be used as an extra measure in screening,
given that they would show a delay in nerve conduction on
the side affected. However, the imaging test of choice is
nuclear magnetic resonance (NMR), which detects tumours
of up to 1 mm in diameter. In this test, neurinomas appear
as lesions in the region of the internal auditory canal with
variable extension towards the cerebellopontine angle; they
Summary of the Tumours Found in our Series, Specifying Hospital of Origin.
Type
Vestibular schwannoma
Trigeminal schwannoma
Vagal nerve schwannoma
Hospital
HUMV
HUGCDN
CHUIMI
Total
5
1
1
8
-----
2
1
1
15
2
1
CHUIMI: Complejo Hospitalario Universitario Insular Materno Infantil; HUGCDN: Hospital Universitario de Gran Canaria Dr. Negrín; HUMV:
Hospital Universitario Marqués de Valdecilla.
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Literature Review and Population Study of Type 2 Neurofibromatosis
Table 4
153
Tumours in the Otorhinolaryngological Area Described in the Literature in Patients With Neurofibromatosis Type II.
Type
No.
Study
Vestibular schwannoma
>100
Trigeminal schwannoma
57
Vagal nerve schwannoma
Nasal schwannoma
Laryngeal schwannoma
5
3
3
Laryngeal neurofibroma
Olfactory bulb meningioma
Optic nerve meningioma
Tympanum cord neuroma
Facial nerve schwannoma
Glossopharyngeal nerve schwannoma
Spinal nerve meningioma
Spinal nerve schwannoma
Hypoglossal nerve schwannoma
1
1
1
1
1
1
1
1
1
Karajannis et al., 2012,9 Plotkin et al., 2012,10 Carlson
et al., 2012,11 Morales Angulo et al., 1997,12 our series
(HUMV, CHUIMI, HUGCDN)
MacNally et al., 2008,13 Ahn et al., 2002,14 Halefoğlu,
2007,15 Liechty et al., 2007,16 Lee et al., 2010,17 Bosch
et al., 2005,18 Majoie et al., 1999,19 Fisher et al.,
2007,20 our series (HUMV, CHUIMI)
Fisher et al., 2007,20 our series (HUMV, CHUIMI)
O’Brien et al., 2005,21 Butugan et al., 199322
Nagato et al., 2010,23 Li et al., 2007,24 Nishino et al.,
199925
Cihangiroglu et al., 200226
O’Brien et al., 200521
Liechty et al., 200716
Huoh and Cheung, 201027
Kiroğlu et al., 199628
Fisher et al., 200720
Liechty et al., 200716
Fisher et al., 200720
Fisher et al., 200720
CHUIMI: Complejo Hospitalario Universitario Insular Materno Infantil; HUGCDN: Hospital Universitario de Gran Canaria Dr. Negrín; HUMV:
Hospital Universitario Marqués de Valdecilla.
are of isointense or slightly hypointense signal in T1, hyperintense in T2 and present intense enhancement following
gadolinium administration. When there is strong suspicion,
gadolinium-enhanced NMR with millimetric cuts on the auditory canal axis can detect sub-millimetric tumours. In cases
of intolerance or impossibility of performing a NMR, highresolution computed tomography (CT) is an alternative.33
Patients with NF-II should also have cervical, thoracic and
lumbar NMR studies to search for other tumours typical of
this disease.34
NF-II is an autosomal dominant disease, with a risk of
appearance in descendents of 50%. Of the patients diagnosed, 50% show a family history of NF-II and the other half
are sporadic cases. The presentation form is similar among
affected family members. The likelihood of NF-II in asymptomatic relatives is low; however, screening by gene study
or NMR is recommended.35
The gene responsible for NF-II is located in the chromosome 22q12.2. This gene codifies a tumour suppressor
protein called merlin or schwannomin, in charge of negative
regulation of the production Schwann cells. Mutation of this
gene predisposes to the appearance of schwannomas when
a second damage is produced to the gene. Various mutations have been identified, including substitution, insertion
and deletion of a single pair of bases. The most common
mutation is the deletion of the gene promoter of the gene
NF-II, exon 1 and intron 1, as well as complete deletions
of the gene.36 In one of the cases in our series, we were
able to confirm the existence of heterozygosis of the mutation IVS12.2A>G in intron 12 of the NF-II gene (22q12) in a
patient with family history.
The appearance of NF-II is not limited to genetic
inheritance: genetic mosaicism frequently occurs35 (in an
estimated 20%---30% of patients without family history),37 in
which the mutation takes place after conception, resulting
in 2 genetically-different cell lines. Most of the people show
a low percentage of cells affected by the mutation; consequently, its detection is impossible using a blood test and
a study of the tumour tissue is needed to study the mutation responsible.35 All of the cases described in our series,
except for 2, are of new appearance, without family history
of NF-II.
Within the clinical picture of NF-II, vestibular schwannomas are usually those with the greatest repercussion on
a patient’s quality of life. Given that patients can show
non-specific symptoms for a long time, the diagnosis of
the disease can be delayed for several years. Mean age
at diagnosis of NF-II is 25 years. These cases are generally
more difficult to treat than those of sporadic appearance.
This is because they are usually bilateral, histologically
less vascularised and more and lobular, and are sometimes accompanied by other tumours (that can be multiple),
whose treatment can cause a long-term morbidity that
seriously influences patient functionality. When the vestibular tumours are small (<1.5 cm), they can be completely
resected, preserving hearing and function of the facial
nerve; if they are large, it is often only possible to debulk the
lesion, without damaging hearing or the facial nerve. However, the current trend is total extirpation together with
cochlear or brain trunk implantation in the same operation. In tumours smaller than 3 cm, in advanced ages, and in
cases of contraindication or rejection of the surgery, a therapeutic alternative is stereotactic radiosurgery with gamma
knife. The role of external radiotherapy is controversial
because these patients have a greater genetic susceptibility to develop secondary malignant tumours (glioblastoma,
rhabdomyosarcoma and malignant meningiomas).37 Due to
the involvement of the bilateral VIII cranial nerves, the
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154
G. Guerra-Jiménez et al.
Table 5
Otorhinolaryngological Symptoms of Neurofibromatosis Type II Described in the Literature, by Frequency.
Symptom
Percentage (%)
References
Hearing loss
66
Unilateral
75
Bilateral
20
Plotkin et al., 2012,10 Plotkin et al., 2012,12 Ahn et al.,
2002,14 Halefoğlu, 2007,15 Lee et al., 2010,17 Nishino
et al., 1999,25 Huoh and Cheung, 2010,27
Stachowicz-Stencel et al., 201130
Plotkin et al., 2012,10 Halefoğlu, 2007,15 Lee et al.,
2010,17 Stachowicz-Stencel et al., 201130
Plotkin et al., 2012,10 Plotkin et al., 2012,12 Ahn et al.,
2002,14 Nishino et al., 1999,25 Cihangiroglu et al.,
2002,26 Huoh and Cheung, 201027
Non-Specified
Cervical mass
5
10
Imbalance
6
Tinnitus
6
Headache
6
Dysphagia
Dyspnoea
Laryngeal mass
Facial paresis
4
4
4
4
Nasal mass
Facial paralysis
Paresis of hypoglossal nerve
Facial paresthesias
Snoring
Dysphonia
Vertigo
Pneumosinus dilatans
4
2
2
2
2
2
2
2
majority of the patients that undergo treatment suffer
bilateral hearing loss as a sequela. In addition, alteration
of balance and decrease in mobility are frequent due to
the involvement of the VIII cranial nerve, vision and muscle weakness. In our series hearing was rehabilitated in 2
patients: in 1 case from the HUGCDN, with excellent audiological results, and in 1 case from the HUMV, that, in
contrast, obtained scant auditory performance.
Survival of 15 years following the diagnosis has been
established, at the mean age of 36 years.38---40 The 2 patients
that died and are documented in our series showed a survival
of 17 years and 11 months respectively.
The main prognostic factors are mean age at diagnosis, presence of intracranial meningiomas and treatment
in specialised centres.8 Early diagnosis, multidisciplinary
management in specialised units and improvements in treatment could increase hope and quality of life for these
patients.
Conclusion
NF-II is a rare clinical entity in the Community of Cantabria
and la province de Las Palmas. The ORL symptom most frequently reported in the literature is unilateral hearing loss,
Ahn et al., 2002,14 Halefoğlu, 2007,15 Liechty et al.,
2007,16 Nagato et al., 2010,23 Hoa and Slattery, 201234
Plotkin et al., 2012,12 Lee et al., 2010,17 Nishino et al.,
199925
Halefoğlu, 2007,15 Lee et al., 2010,17 Huoh and Cheung,
201027
Lee et al., 2010,17 Bosch et al., 2005,18 O’Brien et al.,
200521
Nishino et al., 1999,25 Hoa and Slattery, 201234
Nishino et al., 1999,25 Hoa and Slattery, 201234
Nagato et al., 2010,23 Li et al., 2007, 201224
Huoh and Cheung, 2010,27 Stachowicz-Stencel et al.,
201130
O’Brien et al., 2005,21 Butugan et al., 199322
Tibussek et al., 200929
Stachowicz-Stencel et al., 201130
Lee et al., 201017
Cihangiroglu et al., 200226
Cihangiroglu et al., 200226
Lee et al., 201017
Chennupati et al., 200631
followed by the appearance of a cervical mass and imbalance. The most frequent tumour in this disease is acoustic
neurinoma; vagal nerve and trigeminal neurinomas are much
rarer. Early diagnosis, multidisciplinary management in specialised units and improvements in treatment could increase
hope and quality of life for these patients.
Conflict of Interests
The authors have no conflicts of interests to declare.
Acknowledgements
We wish to thank J.A. Berciano Blanco, of the NRL service
at the Hospital Universitario Marqués de Valdecilla (Santander).
Thanks also go to J.T. Quintana Perera and T. Mendoza
Rodríguez, of the ORL service at the Complejo Hospitalario
Universitario Insular Materno Infantil (Las Palmas de Gran
Canaria).
We are also grateful to Antonio Falcón Rodríguez, of the
records service at the Complejo Hospitalario Universitario
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Literature Review and Population Study of Type 2 Neurofibromatosis
Insular Materno Infantil (Las Palmas de Gran Canaria), and
to A. Ramos Pérez (Las Palmas de Gran Canaria).
References
1. Evans DG, Moran A, King A, Saeed S, Gurusinghe N, Ramsden
R. Incidence of vestibular schwannoma and neurofibromatosis
2 in the North West of England over a 10-year period: higher
incidence than previously thought. Otol Neurotol. 2005;26:
93---7.
2. Evans DG, Howard E, Giblin C, Clancy T, Spencer H, Huson
SM, et al. Birth incidence and prevalence of tumor-prone syndromes: estimates from a UK family genetic register service.
Am J Med Genet A. 2010;152A:327---32.
3. Antinheimo J, Sankila R, Carpén O, Pukkala E, Sainio M,
Jääskeläinen J. Population-based analysis of sporadic and type 2
neurofibromatosis-associated meningiomas and schwannomas.
Neurology. 2000;54:71---6.
4. UpToDate. Evans DG. Neurofibromatosis type 2 [sede Web].
[accessed 11 May 2013]. Waltham, Massachusetts; 2013. Available from: http://www.uptodate.com/
5. Neurofibromatosis. Conference statement. National Institutes
of Health Consensus Development Conference. Arch Neurol.
1988;45:575---8.
6. Evans DG. Neurofibromatosis 2 (Bilateral acoustic neurofibromatosis, central neurofibromatosis, NF2, neurofibromatosis
type II). Genet Med. 2009;11:599---610.
7. Baser ME, Friedman JM, Joe H, Shenton A, Wallace AJ,
Ramsden RT, et al. Empirical development of improved diagnostic criteria for neurofibromatosis 2. Genet Med. 2011;13:
576---81.
8. Pérez-Grau M, Miró N, Prades J, Vergés J, Lareo S, RocaRibas F. Neurofibromatosis tipo 2. Acta Otorrinolaringol Esp.
2010;61:306---11.
9. Karajannis MA, Legault G, Hagiwara M, Ballas MS, Brown K, Nusbaum AO, et al. Phase II trial of lapatinib in adult and pediatric
patients with neurofibromatosis type 2 and progressive vestibular schwannomas. Neuro Oncol. 2012;14:1163---70.
10. Plotkin SR, Merker VL, Halpin C, Jennings D, McKenna MJ,
Harris GJ, et al. Bevacizumab for progressive vestibular schwannoma in neurofibromatosis type 2: a retrospective review of
31 patients. Otol Neurotol. 2012;33:1046---52.
11. Carlson ML, Breen JT, Driscoll CL, Link MJ, Neff BA, Gifford
RH, et al. Cochlear implantation in patients with neurofibromatosis type 2: variables affecting auditory performance. Otol
Neurotol. 2012;33:853---62.
12. Morales Angulo C, del Valle Zapico A, Rubio Suárez A, Mazón
Gutiérrez A, Rama Quintela J. Differential diagnosis of bilateral progressive sensorineural loss. A report of a case secondary
to neurofibromatosis 2. Acta Otorrinolaringol Esp. 1997;48:
400---4.
13. MacNally SP, Rutherford SA, Ramsden RT, Evans DG, King
AT. Trigeminal schwannomas. Br J Neurosurg. 2008;22:
729---38.
14. Ahn JY, Kwon SO, Shin MS, Shim JY, Kim OJ. A case of multiple schwannomas of the trigeminal nerves, acoustic nerves,
lower cranial nerves, brachial plexuses and spinal canal:
schwannomatosis or neurofibromatosis? Yonsei Med J. 2002;43:
109---13.
15. Halefoğlu AM. Neurofibromatosis type 2 associated with multiple cranial nerve schwannomas: a case report. Kulak Burun
Bogaz Ihtis Derg. 2007;17:171---5.
16. Liechty P, Tubbs RS, Loukas M, Blount JP, Wellons JC,
Acakpo-Satchivi L, et al. Spinal accessory nerve meningioma
in a paediatric patient: case report. Folia Neuropathol.
2007;45:23---5.
155
17. Lee HH, Lian SL, Huang CJ, Huang MY. Tomotherapy for neurofibromatosis type 2: case report and review of the literature. Br
J Radiol. 2010;83:e74---8.
18. Bosch MM, Mironov A, Killer HE. Atypical manifestation of
neurofibromatosis type 2 in a boy. Eye (Lond). 2005;19:
705---6.
19. Majoie CB, Hulsmans FJ, Castelijns JA, Sie LH, Walter A,
Valk J, et al. Primary nerve-sheath tumours of the trigeminal nerve: clinical and MRI findings. Neuroradiology. 1999;41:
100---8.
20. Fisher LM, Doherty JK, Lev MH, Slattery 3rd WH. Distribution of
nonvestibular cranial nerve schwannomas in neurofibromatosis
2. Otol Neurotol. 2007;28:1083---90.
21. O’Brien DF, Farrell M, Pidgeon CN. Combined nasal and skull base
pathology: adjacent nasal schwannoma and olfactory groove
meningioma. Br J Neurosurg. 2005;19:446---8.
22. Butugan O, Grasel SS, de Almeida ER, Miniti A. Schwannoma of
the nasal septum. Apropos of 2 cases. Rev Laryngol Otol Rhinol
(Bord). 1993;114:33---6.
23. Nagato T, Katada A, Yoshizaki T, Kunibe I, Takahara M, Katayama
A, et al. Laryngeal plexiform schwannoma as first symptom in a
patient with neurofibromatosis type 2. Clin Neurol Neurosurg.
2010;112:505---8.
24. Li XS, Wang X, Zhao HF. Neurofibromatosis II with large schwannoma of larynx in a case. Zhonghua Er Bi Yan Hou Tou Jing Wai
Ke Za Zhi. 2007;42:542---3.
25. Nishino H, Ishikawa K, Ishida T, Kitamura K. A case of laryngeal neurinoma with neurofibromatosis 2. Auris Nasus Larynx.
1999;26:95---9.
26. Cihangiroglu M, Yilmaz S, Topsakal C, Gok U, Altinsoy B,
Cobanoglu B. Laryngeal neurofibroma associated with neurofibromatosis type 2. AJNR Am J Neuroradiol. 2002;23:1637---9.
Available from: http://www.ajnr.org/content/23/10/1637.
long%20-%20aff-2
27. Huoh HC, Cheung SW. Chorda tympani neuroma. Otol Neurotol.
2010;31:1172---3.
28. Kiroğlu MM, Zorludemir S, Süleymanova D. Bilateral acoustic
neurofibromatosis with bilateral multicentric facial schwannomas. Eur Arch Otorhinolaryngol. 1996;253:305---8.
29. Tibussek D, Hübsch S, Berger K, Schaper J, Rosenbaum T, Mayatepek E. Infantile onset neurofibromatosis type 2 presenting
with peripheral facial palsy, skin patches, retinal hamartoma
and foot drop. Klin Padiatr. 2009;221:247---50.
30. Stachowicz-Stencel T, Synakiewicz A, Bien E, AdamkiewiczDrozynska E, Wybieralska-Dubaniewicz M, Balcerska A. Multiple
primary cranio-spinal tumours in a 13-year-old female with neurofibromatosis type 2 management strategy. Childs Nerv Syst.
2011;27:175---8.
31. Chennupati SK, Schipor I, Mirza N. Microdebrider decompression of schwannoma: a novel method of excising a neck mass.
Laryngoscope. 2006;116:2086---8.
32. Vauterin T, Mombaerts I, Jorissen M, Sciot R, Legius E. Pneumosinus dilatans and orbital meningioma in neurofibromatosis
type 2. B-ENT. 2005;1:89---92.
33. UpToDate. Park J, McLaren O, Vernick D, Ramakrishna N.
Vestibular schannoma [sede Web]. [accessed 7 Jul 2013].
Waltham, Massachusetts; 2013. Available from: http://www.
uptodate.com/
34. Hoa M, Slattery W. Neurofibromatosis 2. Otolaryngol Clin North
Am. 2012;45:315---32.
35. Asthagiri AR, Parry D, Butman JA, Kim HJ, Tsilou ET, Zhuang Z,
et al. Neurofibromatosis type 2. Lancet. 2009;373:1974---86.
36. Evans DG. Neurofibromatosis type 2 (NFII). Orphanet J Rare Dis.
2009;4:16.
37. Blakeley JO, Evans DG, Adler J, Brackmann D, Chen R, Ferner
RE, et al. Consensus recommendations for current treatments
and accelerating clinical trials for patients with neurofibromatosis type 2. Am J Med Genet A. 2012;158A:24---41.
Documento descargado de http://www.elsevier.es el 19/11/2016. Copia para uso personal, se prohíbe la transmisión de este documento por cualquier medio o formato.
156
38. Evans DG, Huson SM, Donnai D, Neary W, Blair V, Newton V,
et al. A clinical study of type 2 neurofibromatosis. Q J Med.
1992;84:603---18.
39. Evans DG, Huson SM, Donnai D, Neary W, Blair V, Teare D, et al.
A genetic study of type 2 neurofibromatosis in the United Kingdom. I. Prevalence, mutation rate, fitness, and confirmation
G. Guerra-Jiménez et al.
of maternal transmission effect on severity. J Med Genet.
1992;29:841---6.
40. Evans DG, Huson SM, Donnai D, Neary W, Blair V, Newton V,
et al. A genetic study of type 2 neurofibromatosis in the United
Kingdom. II. Guidelines for genetic counselling. J Med Genet.
1992;29:847---52.